Inflammation is the foundation for cancer and degenerative/autoimmune diseases. Small changes in diet and exercise, e.g. omega-3 oils, vitamin D, low starch, and maintaining muscle mass, can dramatically alter predisposition to disease and aging, and minimize the negative impact of genetic risks. Based on my experience in biological research, I am trying to explain how the anti-inflammatory diet and lifestyle combat disease. 190 more articles at http://coolinginflammation.blogspot.com

Anti-Inflammatory Diet

All health care starts with diet. My recommendations for a healthy diet are here:

Friday, June 12, 2009

My interest is the molecular basis of inflammation, how inflammation is triggered and how inflammation contributes to numerous diseases. I try to expose the inflammatory underpinnings of various diseases by initially linking a disease to inflammation and then unraveling the molecular events that lead to and make up the disease.

How Do I Link a Disease to Inflammation?

My first task is to check the biomedical literature to see if there are research articles that support anti-inflammatory interventions that prevent or limit the disease. I just do a PubMed search the disease name plus anti-inflammatory treatments, e.g. omega-3 fish oils, vitamin D, NSAIDs, etc. It is also possible to see if a disease, such as diabetes, that produces chronic inflammation is a risk factor for the new disease being examined. It is shocking to me that omega-3 fish oils (EPA/DHA) or even flax seed oil, have been found to be effective treatments for numerous diseases that range from allergies, arthritis, inflammatory bowel diseases, depression and even septic shock and multiple organ failure. Aspirin has been used to treat infertility and post partum depression, and at high levels to treat cancer.

Dietary Suppression as Prima Fascia Evidence of Inflammatory Cause

If I find that omega-3 oils have been used successfully to treat a disease, then I attempt to link inflammation to the molecular events that initiate the disease. The biomedical literature is of minimal help here. [Biomedical research is usually limited to assessing the impact of drugs on the symptoms of diseases, so the biomedical literature typically does not provide information on the cause of diseases or ways to cure diseases. Causes and cures do not receive research funding.] I have to learn the basic workings of the organs involved and the alterations of function associated with the disease. I have also found by long experience, that major molecular components are systematically missing from typical explanations of function.

Heparan sulfate/heparin Is Missing in Action

Heparan sulfate proteoglycans (HSPGs) dominate the extracellular environment and yet they are systematically excluded from biomedical research. On this blog, I have provided dozens of examples of the essential role played by HSPGs and disruption of these roles by heparin. The majority of cytokines, growth factors, clotting events, complement cascades and even lipid transport (LDL) act via HSPGs. Leaking of proteins into the urine, across the intestines or the blood brain barrier is controlled by HSPGs, is reduced by inflammation and can be partially repaired by heparin. Autoimmune and allergic diseases are initiated by disruptions in HSPG metabolism. Viral and bacterial pathogens bind to human cells via HSPGs. Cancer cells reduce their HSPGs and start to secrete heparanase in order to metastasize. Mast cells secrete heparin! HSPGs and heparin are major players in tissue function and yet the major cell biology text book does not even discuss them. HSPGs are not mentioned in medical school training even though heparin is the most commonly administered drug.

One of the insights that I bring to my conceptualization of diseases is the role of heparan/heparin in cellular physiology. It explains a lot.

Check for Inflammatory Symptoms by Trying the Anti-Inflammatory Diet

If your symptoms are due to inflammation, there is an easy way to find out. Since diet is the biggest source of inflammation and most of the cells of the immune system congregate in your intestines, it makes sense to check to see your health problems are rooted in inflammation by making simple changes in your diet. Since this is just a test, don’t worry about whether or not this is diet for the rest of your life. Just stick to it for a week and see if it changes your life.The Basic Anti-Inflammatory Diet and Lifestyle Guidelines are here.

(Vitamin D and omega-3 fish oil amounts are minimal levels. More severe examples of inflammation will require higher levels. Vitamin D up to 10,000 IU per day has been found safe. Some individuals require up to 12 fish oil capsule per day to experience relief from symptoms. Increases should be gradual over weeks of time.)

Try it for a week and let me know if your symptoms disappear. The prevalence of diet-based inflammation, makes me confident that you will be glad that you tried these simple, healthy changes. For immediate relief of pain, see my articles on capsaicin, castor oil and menthol/Vicks.

This is not medical advice and is used only in appropriate support of primary medical care.

19 comments:

BTW, the link in your article to "The Basic Anti-Inflammatory Diet and Lifestyle Guideline" seems to be broken. (Looks like there's an extra "http" in there.)

You mention that "some individuals require up to 12 fish oil capsule per day to experience relief from symptoms." Do you know if there is any research on a safe upper limit for fish oil consumption? Are any kinds of fish oil known to be more effective (or less contaminated) than others? For example, some people claim krill oil to be superior to fish oil. From an anti-inflammatory point of view, are such claims justified?

Thanks again for your blog, and keep up the good work with your research and writing. It's great that this information is finally coming to light.

Tom,Sorry about the link.I think that fish oil is well tolerated and I would expect that the amount needed to keep symptoms under control is less than is needed to initially stop them. There are lots of claims about contaminants in fish oil. I don't think that it matters what the contaminants are for the first bottle, but it may make sense to find some refined EPA/DHA after you see if it is effective for you. From what I have read, getting omega-3s from oily fish is safe, because the selenium in the fish minimizes the heavy metal impact. Capsules are easiest to test.

The krill oil also has astaxanthin, which is touted as an antioxidant. I think that it is also an anti-inflammatory compound in its own right, but its target of action has not been identified. Krill oil is more potent than fish oil DHA/EPA. It is one of those things where different people will get different results.

In the diet, I think that vitamin D is most important, followed by carb control, decreased omega-6, increased omega-3, vitamin C, etc. Gradually increasing vitamin D and then omega-3 fish oils, should eliminate most inflammatory symptoms.

BACKGROUND: Sepsis and septic shock syndrome are the leading causes of death incritically ill patients. Lipopolysaccharide (LPS) released by the colonicmicroorganisms may translocate across a compromised lumen, leading to upregulatedreactive oxidative stress, inflammation, and sepsis. The authors examined anenteral formula high in cysteine (antioxidant precursor), omega-3 fatty acids,eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and prebioticfructooligosaccharides (FOS) against systemic inflammatory syndrome. METHODS:Rats were allocated to (1) standard soy-based diet high in cysteine and crudefiber and devoid of EPA-DHA (CHOW); (2) whey-peptide-based liquid diet high incysteine, EPA-DHA, and FOS (CYSPUFA); or (3) casein-based liquid isonitrogenousdiet, low in cysteine and devoid of EPA-DHA-FOS (CASN). Liquid diets provided 25%and CHOW, 23% of calories as protein. After 6 days on diets, rats received anintraperitoneal injection of LPS or saline. Animals gained weight on theirrespective diets and lost weight after LPS administration. The CYSPUFA group lostconsiderably less weight (vs CASN or CHOW, P < .05). Inflammatory cytokinessignificantly increased by 4 hours and subsided 18 hours after assault. The CASN group showed elevated liver enzyme alanine aminotransferase release from damaged hepatocytes and developed severe hepatic pathology with low hematocrit. The CHOW group developed more severe hepatic lesions compared with those on liquid diets. Concentration of liver enzyme and pathology were improved in rats receivingCYSPUFA.

Cristian,That article (JPEN J Parenter Enteral Nutr. 2009 Jul-Aug;33(4):380-9. Epub 2009 Apr 14) illustrates my point of the intimate role of inflammation in disease symptoms. Also note that whey, used in the CYSPUFA diet, is rich in lactoferrin, a potent antibacterial agent. Lactoferrin is hydrolyzed to lactoferricin, an antibacterial peptide, by stomach enzymes. The supportive role of gut flora is also suggested by the successful inclusion of prebiotics. PUFAs have also been used in people and they reduce sepsis deaths by half.

BACKGROUND: A Paleolithic diet has been suggested to be more in concordance with human evolutionary legacy than a cereal based diet. This might explain the lower incidence among hunter-gatherers of diseases of affluence such as type 2diabetes, obesity and cardiovascular disease. The aim of this study was toexperimentally study the long-term effect of a Paleolithic diet on risk factorsfor these diseases in domestic pigs. We examined glucose tolerance,post-challenge insulin response, plasma C-reactive protein and blood pressureafter 15 months on Paleolithic diet in comparison with a cereal based swine feed.METHODS: Upon weaning twenty-four piglets were randomly allocated either tocereal based swine feed (Cereal group) or cereal free Paleolithic diet consistingof vegetables, fruit, meat and a small amount of tubers (Paleolithic group). At17 months of age an intravenous glucose tolerance test was performed and pancreasspecimens were collected for immunohistochemistry. Group comparisons ofcontinuous variables were made by use of the t-test. P < 0.05 was chosen forstatistical significance. Simple and multivariate correlations were evaluated by use of linear regression analysis. RESULTS: At the end of the study thePaleolithic group weighed 22% less and had 43% lower subcutaneous fat thicknessat mid sternum. No significant difference was seen in fasting glucose betweengroups. Dynamic insulin sensitivity was significantly higher (p = 0.004) and the insulin response was significantly lower in the Paleolithic group (p = 0.001).The geometric mean of C-reactive protein was 82% lower (p = 0.0007) andintra-arterial diastolic blood pressure was 13% lower in the Paleolithic group (p= 0.007). In evaluations of multivariate correlations, diet emerged as thestrongest explanatory variable for the variations in dynamic insulin sensitivity,insulin response, C-reactive protein and diastolic blood pressure when comparedto other relevant variables such as weight and subcutaneous fat thickness at mid sternum. There was no obvious immunohistochemical difference in pancreatic isletsbetween the groups, but leukocytes were clearly more frequent in sampled pancreasfrom the Cereal group. CONCLUSION: This study in domestic pigs suggests that aPaleolithic diet conferred higher insulin sensitivity, lower C-reactive proteinand lower blood pressure when compared to a cereal based diet.

Hi, your recommendations for the anti-inflammatory are excellent. Recently, I came across other grain articles which seem to also suggest (thank you Don) the effects of modern agriculture and cereal grains (wheat, gluten, corn, rice) on lowering serum vitamin D concentrations.

Personally over the last 12mos I've had progestin excess from a drug LNg. My main difficulty waiting to get it out of the system b/c it appears stuck in the adipose. Synthetics hormones appear as evil/toxic as omega-6 PUFAs! LNg in the literature raises hsCRP, 2nd phase insulin, glucoses, heart rates, BPs, fluid retention, and a host of hormonal derangements... I think exposure to ALL unnatural hormone-like substances are best avoided if possible for the ultimate anti-inflammatory lifestyle.

How does an anti-inflammatory diet and supplements (fish oil, Vit D, Astaxanthin, etc.)impact muscular inflammation as a result of strength exercising? Since the muscular inflammation is part of the healing repair and muscle growth process, would an anti-inflammatory diet, supplements slow the healing process?

Researchers found that adding tart cherries to your diet may help reduce your risk of cardiovascular disease and metabolic syndrome. The study fed mice one of two diets: a high fat, moderate carbs diet (45% calories from fat, 40% calories from carbs) OR a low fat, high carbs diet (10% calories from fat, 75% calories from carbs).

Mice that were given added cherry powder to either diet had an 11% reduction in cholesterol after three months. In addition, the mice who had cherry powder had 54% body fat compared to 63% body fat in the mice that did not eat cherry powder. Most of the fat reduction was around the belly area of the mice.

The mice that ate cherry also had a 40% reduction in the TNF-alpha inflammation marker and 31% reduction in the IL-6 inflammation marker. The researchers found that “the activity of the genes producing these two compounds was reduced in the mice, suggesting that tart cherries may reduce inflammation at a systemic level.”

BACKGROUND: Numerous antioxidant and anti-inflammatory agents have beenidentified in tart cherries. OBJECTIVE: To test the efficacy of a tart cherryjuice blend in preventing the symptoms of exercise induced muscle damage.METHODS: This was a randomised, placebo controlled, crossover design. Fourteenmale college students drank 12 fl oz of a cherry juice blend or a placebo twice aday for eight consecutive days. A bout of eccentric elbow flexion contractions (2x 20 maximum contractions) was performed on the fourth day of supplementation.Isometric elbow flexion strength, pain, muscle tenderness, and relaxed elbowangle were recorded before and for four days after the eccentric exercise. Theprotocol was repeated two weeks later with subjects who took the placeboinitially, now taking the cherry juice (and vice versa). The opposite armperformed the eccentric exercise for the second bout to avoid the repeated boutprotective effect. RESULTS: Strength loss and pain were significantly less in thecherry juice trial versus placebo (time by treatment: strength p<0.0001, pain p =0.017). Relaxed elbow angle (time by treatment p = 0.85) and muscle tenderness(time by treatment p = 0.81) were not different between trials. CONCLUSIONS:These data show efficacy for this cherry juice in decreasing some of the symptomsof exercise induced muscle damage. Most notably, strength loss averaged over the four days after eccentric exercise was 22% with the placebo but only 4% with the cherry juice.

[Please post just your comments with the PubMed ID number or citation and not the whole summary.]

A high carb diet is inflammatory and cereal is a terrible way to start the day.

Tart cherry anti-oxidants:I wrote an article about my thoughts on antioxidants. Measuring antioxidant potential in food gives an indication of only a minor impact the food components. Chemicals with antioxidant activity also bind directly to hundreds of different proteins with numerous alterations of activities. Eating tart cherry extract and then checking the effects merely shows the sum of all of these interactions and may vary dramatically with gut flora, other diet components, degree of chronic inflammation, etc.

The bottom line is just that some food contribute to chronic inflammation and others tend to reduce it.

Thanks for your continuing interest in my thoughts on inflammation and health.Art

Anonymous,Thanks for your question on inflammation and muscle growth in response to exercise.

Several studies show that NSAIDS, for example, lower the inflammation that is produced by exercise and as a consequence decrease muscle growth.

Extreme exercise results in cytokine production similar to infection and then converts into an anti-inflammatory state.

Chronic fatigue is associated with high inflammatory cytokines and benefits from exercise, but in some forms is also associated with abnormal inflammatory cytokine receptor production, making exercise counterindicated.

Older people tend to become increasingly inflamed and also show dramatic muscle growth in response to exercise.

My thinking on anti-inflammatory diet and muscle growth, is that the final level of inflammation achieved by the diet is what is important. Different people will have the same diet, but different levels of inflammation. Exercise will change the impact of the diet.

It seems to me that you will have to develop a simple measure of your inflammatory state and determine the optimum level of inflammation for maximum muscle growth.

My impression is that a few people in the body building community understand the relationship between diet, exercise (chronic inflammation level) and muscle growth. The biomedical community (particularly dietitians) is much less sophisticated.

Dr. B G,Sorry that I am so slow. (I was looking at hot springs in the Sawtooth Mountains.)

Your comments on grain and vitamin D brings up numerous points. How do you determine the status of your gut flora and the impact of your diet on your inflammatory status?

I think that we should aspire to self-medication in response to our personal cues of well being (or a painful index finger.) Self-medication should be through what we eat in our next meal and how we exercise before and after that meal.

My personal bias is that hormonal and psychological problems derive from the diet/inflammatory state. (This implies an obvious dysfunction in our nomenclature and inflammation requires a new series of terms.) That means that adjusting the diet can remedy hormonal problems and eliminate much of the impact of environmental estrogens and most other "toxins." This is the flip side of the article that you cite. This means that we need to get over treating the symptoms of hormonal dysfunctions and get down to the cause of the hormonal disruption. My prejudice is that in all cases there will be a substantial dietary contribution to the problem.

Alas, there is no money in treating very lucrative diseases with a printed diet, vitamin D capsules and a bottle of cheap fish oil capsules. The neighborhood nurse could just hand these health kits out to everyone with instructions to use the kit for one week for any health problem. The result would be the collapse of agribusiness and the medical industry, and the elimination of the discussion on the healthcare catastrophe in America.

He's a fervid proponent of the leaky gut-inflammation-CFS-depression connection and the importance of cooling down inflammation.

Neuro Endocrinol Lett. 2007 Aug;28(4):456-62.Not in the mind of neurasthenic lazybones but in the cell nucleus: patients with chronic fatigue syndrome have increased production of nuclear factor kappa beta. PMID: 17693979

Cristian,Thank you so much for the Maes link. I am relatively new to the inflammation literature and Maes seems to have made most of the connections that I have been struggling to make over the last couple of years. It seems almost possible to connect the over/under-production of each inflammatory cytokine in the body or brain with a different disease or symptom......The article is also interesting to me, because it ties in the major inflammatory transcription factor, NFkB with a chronic disease, CFS. My prejudice is that production of transcription factors is set and they are either active or inactive. Producing different amounts is a very different process.

Anonymous,The dose of fish oil is dependent on the amount of omega-6 fatty acids in the diet, usually from vegetable oils. It is the ratio of fish oil to omega-6 oils that matters in reducing inflammation.

I usually just keep increasing the fish oil until the inflammatory symptoms are reduced. In the case of allergies, the inflammation is more indirect and it takes longer for existing antibodies to dissipate. Gut flora is also important, since the allergies are based on an initial combination of inflammation and disfunction of gut-based immunity.

I would experiment with slowly increasing fish oil each week to see how much it takes to reduce symptoms.

I had a terrible bout with inflammation that went on for 8 years. I thought it began with tendenitis in my wrist but now I realize that my metabolism had been spiraling out of my control into insulin resistance before the tendenitis appeared. Long story short, after a number of years of searching for information I found (among other helpful sites) Level One Diet (Or Level1Diet), where after some study I realized that omega3 might be the key to reducing my own inflammation. Again long story short, I wound up ingesting 8 capsules per day, about 4,000 mg combined epa/dha, and my joint pain subsided (immediately at that level) as long as I took every last pill every day. If I didn't, I began to suffer accordingly, quickly.Last year I found a doctor who really did offer help rather than prescriptions, and on my own I found the the Drs. Eades book PROTEIN POWER LIFEPLAN whose diet I adhere to today, and probably always will. I began on the low-carb plan last fall and quickly lost 25 pounds. My blood tests showed that my blood sugar still is slightly high but I wonder if that's from the omega3. I am taking a high level of vitamin D along with a diebetic multivitamin and some other supplements. I'm 66, feel better than when I was 26.

I knew before I found your site that inflammation is the the cause of human disease and that it's the inflammation that we have to pay attention to. I also understand the inflammatory nature of grains and other foods we're commonly exhorted to eat. I'm through with that. I can move so freely without pain, am so comfortable in my body, and feel so good that I will never again listen to any diet dictocrat who prattles about the healthfulness of the sugar that is referred to as carbohydrates. Thank you for this amazing website. I'll be working my way through it bit by bit, sending links to friends who are miserable because they are depending on doctors who only offer prescriptions and no real help.Is it any wonder that our national health care bill is out of control?!Best wishes.Stay healthy.

Have been very sick most of my life (gluten intolerance) but didn't know it. Most recently, with no help from several docs, I began to read and suspected metabolic syndrome. Discovered PROTEIN POWER LIFEPLAN (Eades) and with its help lost 45 pounds. Now HDL is high, triglycerides are low and everything else is right too. I now have the energy I've never had and actually want to run...well, maybe jog. Tried it and nothing fell off or dislocated so will be doing it 3 days per week, starting slowly with a jog one minute/walk one minute routine.Ah, life is so sweet, but I digress.Without 4,000 mg of epa/dha per day my whole inflammation thing becomes active again. X-rays proved (to my endocrinologist) that my hands and feet are riddled with arthritis. My neck crackles and snaps, so do knees, spine, shoulders, but as long as I take enough omega3, I feel wonderful and have no pain, which must mean that the inflammation is held in check. If I cut back by even one 500 mg capsule I soon feel the effects.I'm still on low-carb diet (more or less the Dr. Bernstein plan) and will be for the rest of my life. I need to keep my carbs at around 21 grams per day or I cannot function (and cannot continue to lose body fat). I'm very grateful that I found the Drs. Eades and their book, Gary Taubes and his books, Volek and Phinney and their book, this blogsite and many many others that assisted me to become more self-aware and more aware of my cell chemistry and understand the wonder and implacable demands of my biochemical body. If we eat right, all will be well. Believe it.

I understand there is a huge prevalence of diet-based inflammation in our culture. You address this very thoroughly here on your blog.

What roll does stress play in inflammation? Does it negatively affect our gut flora? I know stress can be very subjective and difficult to measure, and can be emotional, mental, physical or relational in nature, even good stress, and bad stress. But as I understand it, our bodies don't know the difference, so it is all the same, really. It is still stress.

Does the gut flora disruption come first and then the stress, or the stress result in gut flora disruption. All I know is that when I am under a lot of stress, I have many more aches, pains, and inflammatory symptoms. Is there an explanation for this? And in this light, should reduction of stress be on the lifestyle recommendations, for people like me whose health feels negatively affected by stress? Or is this what the vagal nerve stimulation is getting at?

What is your opinion regarding the impact of inflammation on the body's susceptibility to chronic infection? Or vice versa?

A quantitative Marcons test (Multiple Antibiotic Resistant Coagulase Negative Staphylococci) yielded a high level of staph in my sinuses. I have a strong suspicion that this bug is what is contributing to whole body inflammation.

I've read that Vitamin D acts as a natural antibiotic (BTW, my level is low at 17 ng/dl) and that Vitamin D activates a cell receptor that activates cathelicidin, which is involved in killing of intracellular bacteria.

Theoretically, could increasing Vitamin D levels thwart off this opportunistic bug by strengthening the immune system? So tired of trying anti-microbials, which seem to fail me, without a strong immune system in place to begin with.

Listen to my podcast on Jimmy Moore's Livin' La Vida Low Carb Show

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About Me

I grew up in San Diego and did my PhD in Molecular, Cellular and Developmental Biology (U. Colo. Boulder). I subsequently held postdoctoral research positions at the Swedish Forest Products Research Laboratories, Stockholm, U. Missouri -Colombia and Kansas State U. I was an assistant professor in the Cell and Developmental Biology Department at Harvard University, and an associate professor and Director of the Genetic Engineering Program at Cedar Crest College in Allentown, PA. I joined the faculty at the College of Idaho in 1991 and in 1997-98 I spent a six-month sabbatical at the National University of Singapore. Most recently I have focused on the role of heparin in inflammation and disease.